The primary aim of this proposal is to develop a model for studying brain metabolism in vivo in an animal phylogenetically close to man. The animal will be the chair-restrained adolescent male baboon, which will have permanently implated catheters in the carotid artery, ipsolateral sigmoid sinus and femoral vein and artery. Studies will be performed in the unanesthetized state. Brain arteriovenous differences will be assessed by withdrawing blood from the femoral artery and sigmoid sinus. Brain blood flow will be measured by injecting a bolus of hydrogen-saturated saline in the carotid artery and determining subsequent changes in hydrogen concentrations in the sigmoid sinus. This animal model will be utilized to: 1. Document serial changes in brain fuel and amino acid flux during fasting. 2. Correlate changes in fuel and amino acid metabolism with arterial concentrations of fuel and brain turnover of neurotransmitters (e.g., serotonin). 3. Infuse ketone bodies via a carotid artery catheter into the brain and assess the effect on glucose uptake and oxidation. 4. Assess the effect of amino acid infusions on amino acid flux, arterial hormone levels and neurotransmitter turnover. 5. Induce diabetic ketoacidosis with streptozotocin and evaluate in terms of brain oxygen concumption, fuel metabolism, and red cell 2,3, DPG levels: a. changes in consciousness and b. effect of treatment with phosphate, bicarbonate and hypoglycemic doses of insulin.